The broad objective of this proposal is the continued development of a program in inhalation or pulmonary toxicology. It is intended to apply to selected substances and to realistic mixtures a methodological approach designed to provide sufficient and appropriate data on the pharmacokinetic constants of an inhaled atmosphere to permit a degree of prediction of the disposition of an inhaled dose, an estimate of probable toxicity and a reasonable basis for investigation of the mechanisms of toxic effects. For a given toxicant or mixture it is planned to examine the following: (a) compartmental distribution with time after inhalation, (b) rates of excretion of parent compound and when applicable, distribution and excretion of metabolites, (c) occurrence and interaction of initial effects particularly in alveolar regions. Compounds and mixtures will be selected on the basis of realistic hazard and the need for re-evaluation. Initial studies will center on pesticides starting with chlorinated phenols, particularly pentachlorophenol, alone or in combination with insoluble particulate material.